Characterization of T cell responses to co-administered hookworm vaccine candidates Na-GST-1 and Na-APR-1 in healthy adults in Gabon.

Autor: Mouwenda YD; Centre de Recherches Médicales de Lambaréné (CERMEL), Lambaréné, Gabon.; Department of Parasitology, Leiden University Medical Center (LUMC), Leiden, The Netherlands., Betouke Ongwe ME; Centre de Recherches Médicales de Lambaréné (CERMEL), Lambaréné, Gabon.; Department of Parasitology, Leiden University Medical Center (LUMC), Leiden, The Netherlands.; Centre National de la Recherche Scientifique et Technologique (IRET- CENAREST), Libreville, Gabon., Sonnet F; Department of Parasitology, Leiden University Medical Center (LUMC), Leiden, The Netherlands., Stam KA; Department of Parasitology, Leiden University Medical Center (LUMC), Leiden, The Netherlands., Labuda LA; Department of Parasitology, Leiden University Medical Center (LUMC), Leiden, The Netherlands., De Vries S; Centre de Recherches Médicales de Lambaréné (CERMEL), Lambaréné, Gabon.; Center of Tropical Medicine and Travel Medicine, Department of Infectious Diseases, Division of Internal Medicine, Amsterdam University Medical Center, (AMC), University of Amsterdam, Amsterdam, the Netherlands., Grobusch MP; Centre de Recherches Médicales de Lambaréné (CERMEL), Lambaréné, Gabon.; Center of Tropical Medicine and Travel Medicine, Department of Infectious Diseases, Division of Internal Medicine, Amsterdam University Medical Center, (AMC), University of Amsterdam, Amsterdam, the Netherlands.; Institut für Tropenmedizin, Universität Tübingen, Tübingen, Germany., Zinsou FJ; Centre de Recherches Médicales de Lambaréné (CERMEL), Lambaréné, Gabon.; Institut für Tropenmedizin, Universität Tübingen, Tübingen, Germany., Honkpehedji YJ; Centre de Recherches Médicales de Lambaréné (CERMEL), Lambaréné, Gabon.; Institut für Tropenmedizin, Universität Tübingen, Tübingen, Germany., Dejon Agobe JC; Centre de Recherches Médicales de Lambaréné (CERMEL), Lambaréné, Gabon.; Center of Tropical Medicine and Travel Medicine, Department of Infectious Diseases, Division of Internal Medicine, Amsterdam University Medical Center, (AMC), University of Amsterdam, Amsterdam, the Netherlands.; Institut für Tropenmedizin, Universität Tübingen, Tübingen, Germany., Diemert DJ; Department of Microbiology, Immunology and Tropical Medicine, School of Medicine and Health Sciences, The George Washington University, Washington, District of Columbia, United States of America., van Leeuwen R; Amsterdam Institute for Global Development (AIGHD), Amsterdam, The Netherlands., Bottazzi ME; Texas Children's Hospital Center for Vaccine Development, Departments of Pediatrics and Molecular Virology and Microbiology, National School of Tropical Medicine, Baylor College of Medicine, Houston, Texas, United States of America., Hotez PJ; Texas Children's Hospital Center for Vaccine Development, Departments of Pediatrics and Molecular Virology and Microbiology, National School of Tropical Medicine, Baylor College of Medicine, Houston, Texas, United States of America., Kremsner PG; Centre de Recherches Médicales de Lambaréné (CERMEL), Lambaréné, Gabon.; Institut für Tropenmedizin, Universität Tübingen, Tübingen, Germany.; German Center for Infection Research, Tübingen, Germany., Bethony JM; Department of Microbiology, Immunology and Tropical Medicine, School of Medicine and Health Sciences, The George Washington University, Washington, District of Columbia, United States of America., Jochems SP; Department of Parasitology, Leiden University Medical Center (LUMC), Leiden, The Netherlands., Adegnika AA; Centre de Recherches Médicales de Lambaréné (CERMEL), Lambaréné, Gabon.; Department of Parasitology, Leiden University Medical Center (LUMC), Leiden, The Netherlands.; Institut für Tropenmedizin, Universität Tübingen, Tübingen, Germany.; German Center for Infection Research, Tübingen, Germany., Massinga Loembe M; Centre de Recherches Médicales de Lambaréné (CERMEL), Lambaréné, Gabon., Yazdanbakhsh M; Department of Parasitology, Leiden University Medical Center (LUMC), Leiden, The Netherlands.
Jazyk: angličtina
Zdroj: PLoS neglected tropical diseases [PLoS Negl Trop Dis] 2021 Oct 01; Vol. 15 (10), pp. e0009732. Date of Electronic Publication: 2021 Oct 01 (Print Publication: 2021).
DOI: 10.1371/journal.pntd.0009732
Abstrakt: Two hookworm vaccine candidates, Na-GST-1 and Na-APR-1, formulated with Glucopyranosyl Lipid A (GLA-AF) adjuvant, have been shown to be safe, well tolerated, and to induce antibody responses in a Phase 1 clinical trial (Clinicaltrials.gov NCT02126462) conducted in Gabon. Here, we characterized T cell responses in 24 Gabonese volunteers randomized to get vaccinated three times with Na-GST-1 and Na-APR-1 at doses of 30μg (n = 8) or 100μg (n = 10) and as control Hepatitis B (n = 6). Blood was collected pre- and post-vaccination on days 0, 28, and 180 as well as 2-weeks after each vaccine dose on days 14, 42, and 194 for PBMCs isolation. PBMCs were stimulated with recombinant Na-GST-1 or Na-APR-1, before (days 0, 28 and 180) and two weeks after (days 14, 42 and 194) each vaccination and used to characterize T cell responses by flow and mass cytometry. A significant increase in Na-GST-1 -specific CD4+ T cells producing IL-2 and TNF, correlated with specific IgG antibody levels, after the third vaccination (day 194) was observed. In contrast, no increase in Na-APR-1 specific T cell responses were induced by the vaccine. Mass cytometry revealed that, Na-GST-1 cytokine producing CD4+ T cells were CD161+ memory cells expressing CTLA-4 and CD40-L. Blocking CTLA-4 enhanced the cytokine response to Na-GST-1. In Gabonese volunteers, hookworm vaccine candidate, Na-GST-1, induces detectable CD4+ T cell responses that correlate with specific antibody levels. As these CD4+ T cells express CTLA-4, and blocking this inhibitory molecules resulted in enhanced cytokine production, the question arises whether this pathway can be targeted to enhance vaccine immunogenicity.
Competing Interests: no authors have competing interests.
Databáze: MEDLINE
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